This is a revised proposal to examine the mechanisms of use-dependent plasticity in the neocortex. The rat somatosensory system is selected for the study because of the strict topography of the afferent pathway: each facial whisker projects as a separate cluster of neurons in layer IV, a cortical "barrel," forming the basis of a column of neurons from layers II to VI. The proposed study is motivated by our previous demonstration that the barrel cortex is modified by changes in sensory activity. To alter sensory activity, we clipped all but two whiskers on one side of the face. After 3-30 days of "whisker pairing," the receptive fields of layer IV cells were assessed. Neurons in layer IV had a significantly increased response to the intact "paired" whiskers, and a decreased response to the clipped whiskers. The "bias" of layer IV cells in favor of the paired whiskers increased progressively throughout the period of whisker pairing. Our hypothesis for this cortical modification starts with the fact that neurons located above and below a given barrel integrate information from many sources: their own barrel, surrounding barrels, the secondary thalamic sensory nucleus POm, and other cortical somatosensory areas such as S-II. Since they are the sites of multiwhisker convergence, we propose that supragranular (SGR) and infragranular (IGR) neurons are highly sensitive to any change in the pattern of afferent activity: the receptive fields of these neurons are shaped by a "bias" in whisker use after just a few hours. In subsequent days, the neurons in the IGR and SGR layers confer the bias on layer IV barrel ells, leading to long-term modifications in the functional linkage between barrels. The first step is to test the prediction that neurons in the non-GR layers are highly sensitive to shifts in sensory activity by comparing the modifiability of the different cortical layers after a 24-hour period of whisker pairing. This study has been completed since the original grant submittal (in press, Science) and no longer constitutes a Specific Aim. The result was that the cortical column is not transformed as a homogenous unit: neurons in the SGR and IGR layers of column D2 exhibited significant plasticity after a brief period of whisker pairing, at a time when GR neurons showed no adaptation to the change in experience. These findings strongly support the main thesis and form the basis for the subsequent aims. The next step, therefore, will be to assess the contribution of the SGR layers to layer IV plasticity. This will be accomplished using a method that selectively ablates layers I-III, leaving layers IV-VI intact. Finally, the role of 'parallel' sensory inputs to barrel cortex will be examined. Neurons in the thalamic posterior complex (POm) and the secondary somatosensory cortex (S-II) respond to whisker deflection, and their axons terminate above and below layer IV, avoiding the barrels. To test the idea that POm and S-II are essential for use-dependent plasticity, we will measure the response of barrel cortex to whisker pairing after selectively ablating one or both areas. Determining the mechanisms of experience-dependent plasticity in barrel cortex will provide insights into the physiological bases of learning and memory, as well as the reaction of the neocortex to peripheral or central nervous system trauma.